The role of thymic tolerance in CNS autoimmune disease

The contributions of the peripheral adaptive and innate immune systems to CNS autoimmunity have been extensively studied. However, the role of thymic selection in these conditions is much less well understood. The thymus is the primary lymphoid organ for the generation of T cells; thymic mechanisms ensure that cells with an overt autoreactive specificity are eliminated before they emigrate to the periphery and control the generation of thymic regulatory T cells. Evidence from animal studies demonstrates that thymic T cell selection is important for establishing tolerance to autoantigens. However, there is a considerable knowledge gap regarding the role of thymic selection in autoimmune conditions of the human CNS. In this Review, we critically examine the current body of experimental evidence for the contribution of thymic tolerance to CNS autoimmune diseases. An understanding of why dysfunction of either thymic or peripheral tolerance mechanisms rarely leads to CNS inflammation is currently lacking. We examine the potential of de novo T cell formation and thymic selection as novel therapeutic avenues and highlight areas for future study that are likely to make these targets the focus of future treatments

Physical Activity Promotion in Primary Health Care in Brazil: A Counseling Model Applied to Community Health Workers

Background:The aim of this study was to describe a methodology for training to provide counseling on physical activity among community health workers working within primary healthcare in Brazil.Methods:This was an intervention study conducted with 65 community health workers in the Ermelino Matarazzo district in the São Paulo, Brazil (30 in intervention group). The intervention group received a course of 12 hours (with 4 meetings of 3 hours each in 1 month) that aimed to improve their knowledge and be autonomous with regard to promoting physical activity. For data analysis, focus groups and questionnaires on knowledge and perceptions regarding physical activity were used.Results:The average attendance for the 4 meetings was 29 workers (93% of total). There was an improvement in knowledge on physical activity recommendations in comparison with the control (P = .03), and qualitative results revealed that the professionals appreciated the learned content, valued its application based on knowledge construction and felt secure about promoting physical activity. This was seen through high adherence levels and construction collective of proposal for home visits for physical activity promotion.Conclusion:The training was effective in improving knowledge and attitudes toward counseling on physical activity among community health workers.</jats:sec

An Adaptive Finite Time Sliding Mode Observer

This chapter develops a novel adaptive ?nite time observer which can achieve ?nite time unmatched parameter estimation and ?nite time system state observation. The proposed approach has strong robustness and rapid convergence. A step by step proof is given which employs ?nite time stability and sliding mode principles. It is seen that the method also enables lumped matched uncertainty to be estimated. An illustrative example is used to validate the effectiveness of the proposed approach

Quality by design: Scale-up of freeze-drying cycles in pharmaceutical industry

This paper shows the application of mathematical modeling to scale-up a cycle developed with lab-scale equipment on two different production units. The above method is based on a simplified model of the process parameterized with experimentally determined heat and mass transfer coefficients. In this study, the overall heat transfer coefficient between product and shelf was determined by using the gravimetric procedure, while the dried product resistance to vapor flow was determined through the pressure rise test technique. Once model parameters were determined, the freeze-drying cycle of a parenteral product was developed via dynamic design space for a lab-scale unit. Then, mathematical modeling was used to scale-up the above cycle in the production equipment. In this way, appropriate values were determined for processing conditions, which allow the replication, in the industrial unit, of the product dynamics observed in the small scale freeze-dryer. This study also showed how inter-vial variability, as well as model parameter uncertainty, can be taken into account during scale-up calculations